Hemolytic Uremic Syndrome (HUS)

What is the Hemolytic Uremic Syndrome and What Do I Need to Know about It?

Post-diarrheal Hemolytic Uremic Syndrome is a severe, life-threatening complication that occurs in about 10% of those infected with Escherichia coli (E. coli) O157:H7 or other Shiga toxin-producing E. coli.

Post-diarrheal HUS is usually signified as “D+ HUS,” while HUS not preceded by diarrhea is signified as “D- HUS.” (For the ease of reference, we will use HUS throughout this site unless some more specific terminology is needed.)

HUS was first described in 1955, but was not known to be secondary to E. coli infections until 1982. It is now recognized as the most common cause of acute kidney failure in infants and young children. Adolescents and adults are also susceptible, as are the elderly, who often die as a result of the disease.

How did these otherwise harmless E. coli become such killers? It seems likely that DNA from a Shiga toxin producing bacterium known as Shigella dysenteriae type 1 was transferred by a bacteriophage (a virus that infects bacteria) to harmless E. coli bacteria, thereby providing them with the genes to produce one of the most potent toxins known to man—so potent, in fact, that the Department of Homeland Security lists Shiga toxin as a potential bioterrorist agent. Although E. coli O157:H7 are responsible for the majority of cases in America, there are many additional Shiga toxin-producing E. coli strains that can cause HUS.

From Diarrhea to Dialysis

The chain of events leading to HUS begins with the ingestion of Shiga toxin-producing E. coli—for example, E. coli O157: H7—in contaminated food or beverages, or as a result of exposure to animals carrying the bacteria, or from person-to-person transmission.

These E. coli rapidly multiply in the intestine, causing colitis (diarrhea), and tightly bind to cells that line the large intestine. This snug attachment facilitates absorption of the toxin into the intestinal capillaries and into the systemic circulation where it becomes attached to weak receptors on white blood cells, thus allowing the toxin to “ride piggyback” to the kidneys where it is transferred to numerous avid (strong) Gb3 receptors that grasp and then hold on to the toxin.
Organ injury is primarily a function of receptor location and density. The receptors are probably diversely distributed in the major body organs, and this may explain why some patients develop injury in different organs—for example, the brain or pancreas.

Once the Shiga toxins attach to receptors, they move into the interior of the cell (cytoplasm), where the toxins shut down the protein machinery, resulting in cellular injury or death. Injury activates blood platelets and the “coagulation cascade.” This coagulation causes the formation of clots in the very small vessels of the kidney, resulting in acute kidney injury and failure.

The red blood cells are either destroyed by the Shiga toxin (hemolytic destruction), or they are damaged as the cells attempt to pass through partially obstructed microvessels. Blood platelets, which are required for normal blood clotting, become trapped in the tiny blood clots, or they are damaged and destroyed by the spleen.